1. health and fitness
2. disease

VIRAL INFECTIONS
Acute childhood exanthems
measles has decreased since the introduction of comprehensive
immunization programmes from 873,000 deaths in 1999 to
345,000 in 2005.1 Controversial interpretation of small studies
with widespread media reporting have led to a decrease in
uptake of the MMR vaccine in the developed world.2 Subsequently there have been outbreaks of measles in children and
adults resulting from a loss of individual and herd immunity. The
incidence of measles is increasing in the UK with 1348 laboratory-confirmed cases in 2008, almost 40% higher than the 990 in
2007.3 Over 50% of these were nursery and primary school age
children, with about 20% in adults. Unfortunately, despite
numerous studies showing no relationship between MMR and
neurodevelopmental
or
gastrointestinal
disturbances,4e6
currently only 78% of children in the UK have had two doses by
their fifth birthday.7
Measles has a prodromal period of fever, coryza, conjunctivitis and cough for several days before the rash develops. The
morbilliform rash has maculopapular lesions of a few millimetres
that may be confluent (Figure 1). Koplik’s spots are pathognomonic white spots on the buccal mucosa. Complications include
otitis media, pneumonia, pneumonitis, myocarditis and pericarditis. Encephalitis may occur, either acutely, or months to years
later as subacute sclerosing panencephailitis.
Treatment of measles is primarily supportive, although in
immunocompromised individuals intravenous immunoglobulin
(IVIG) and ribavirin have been used to try to decrease the
duration of viraemia.8 Vitamin A supplementation is widely used
to reduce mortality, although a Cochrane review showed that this
was likely to be of most benefit in children under the age of two
years.9 A recent review of the Cochrane database suggested that
concurrent antibiotic treatment may prevent pneumonia and
otitis media.10 The mainstay of secondary prevention comprises
contact tracing with implementation of catch-up immunization
and, in immunocompromised individuals, prophylaxis with
IVIG.
Penelope A Bryant
Mike Sharland
Abstract
Exanthems are skin rashes that in childhood are most commonly caused by
viruses. Measles, rubella, varicella, erythema infectiosum, papularpurpuric gloves and socks syndrome, roseola infantum, hand, foot and
mouth disease, GianottieCrosti syndrome, unilateral laterothoracic
exanthem and pityriasis rosea are discussed. Transmission, infectivity,
prodrome, clinical presentation, complications and treatment are included.
Although it is often difficult to identify the specific virus, polymerase chain
reaction has improved diagnostic accuracy, which is particularly important
in immunocompromised individuals and pregnant women. Alternative
diagnoses include bacterial and non-infectious causes.
Keywords erythema infectiosum; exanthem; measles; rash; roseola;
rubella; varicella; virus
Exanthems are skin rashes that are usually generalized and
associated with systemic symptoms including fever. The
commonest cause in childhood is viral infection although other
causes include bacterial infection and drug exposure. Diagnosis
of the aetiology of a viral exanthem is often difficult, and relies
on relevant history: prodromal symptoms, evolution of the rash,
associated symptoms, exposure to infections, foreign travel, time
of year and immunization history. Examination findings that
guide diagnosis include the nature of the rash, its distribution,
and other manifestations including oral enanthems. Most of the
viral exanthems can be diagnosed serologically or by identifying
viral RNA by polymerase chain reaction (PCR) in blood, respiratory specimens or cerebrospinal fluid.
Viral exanthems are predominantly maculopapular rashes
that may be difficult to distinguish. Although there are
occasionally severe complications, they are generally selflimiting illnesses (Table 1). Specific diagnosis is important in
immunocompromised individuals or if there is exposure to
pregnant women.
Rubella
Caused by a togavirus, rubella (German measles) is spread by
respiratory droplets and is most prevalent in late winter and
spring. In countries with comprehensive childhood immunization and effective catch-up campaigns in adolescence and in
women of child-bearing age there has been a dramatic decrease
in the incidence of rubella.11 However, many countries have no
anti-rubella immunization programmes and globally the
incidence of congenital rubella syndrome is estimated to be over
100,000/year.12
Rubella is an asymptomatic infection in up to 50% of individuals. In symptomatic children there is a mild prodromal febrile
period with lymphadenopathy and conjunctivitis, whereas in
adults the symptoms are usually more prominent with anorexia,
nausea and fever. The prodrome precedes a facial maculopapular
rash that spreads to the trunk and limbs and fades in about three
days. The rash, lymphadenopathy and conjunctivitis may initially
be mistaken for adenoviral infection or Kawasaki’s disease.
Rarely, there are also red papules on the hard palate (Forscheimer’s spots). Complications are unusual, although occasionally adults develop transient arthropathy, and rarely
peripheral neuritis or encephalitis. If a pregnant woman contracts
rubella in the first trimester, transplacental infection can cause
Measles
Caused by a paramyxovirus, measles (rubeola) is spread by
respiratory contact. It remains a significant cause of childhood
mortality in developing countries, although global mortality from
Penelope A Bryant MA BMBCh MRCP MRCPCH PhD is a Consultant in
Paediatric Infectious Diseases in the Paediatric Infectious Diseases Unit
at St George’s Hospital, London, UK. Competing interests: none
declared.
Mike Sharland MD FRCPCH DTM&H is a Consultant in Paediatric Infectious
Diseases in the Paediatric Infectious Diseases Unit at St George’s
Hospital, London, UK. Competing interests: none declared.
MEDICINE 37:12
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Ó 2009 Elsevier Ltd. All rights reserved.
VIRAL INFECTIONS
Incubation and infectivity periods for acute viral exanthems
Exanthem
Incubation (days)
Duration of infectivity
Measles
Rubella
8e12
14e21
Varicella
Erythema infectiosum
Papular-purpuric gloves and
socks syndrome
Roseola infantum
Hand, foot and mouth
10e21
4e14
10
Two days before prodrome to five days after rash appears
Seven days before rash to five days after rash appears; in congenital infection viral shedding
can persist for months
Two days before rash to five days after rash appears
Before the onset of the rash
During shedding of virus, which can persist until after the rash disappears after 7e14 days
9
4e7
During shedding of virus, which can persist for weeks
During shedding of the virus, which can persist in the stool for several weeks
Table 1
congenital rubella syndrome in the developing foetus. This leads
to a high probability of foetal loss or premature birth, and
a constellation of severe symptoms in the baby, including cerebral,
cardiac, ophthalmic and auditory defects. It is a progressive
disease and all abnormalities may not be present at birth.
Rubella vaccine is contraindicated in pregnancy. However, if
a woman is inadvertently vaccinated in the first trimester, this
does not necessarily cause congenital disease and is not an
indication for termination.13
in about 10%. Rarely, the more severe manifestation of group A
streptococcal necrotizing fasciitis occurs, which is characterized
by severe pain.14 This is a surgical emergency and must be
considered in an individual with varicella with these symptoms.
The rate of complications following varicella, such as pneumonitis, encephalitis and cerebellar ataxia, is higher in adults than
in children. Rare complications include transverse myelitis,
nephritis and carditis. In children who are immunocompromised
and who come into contact with varicella, it is possible to avert
development of the disease by giving varicella-zoster specific
immunoglobulin (VZIG) within 72 h of the contact. Owing to the
high viral dose via the placenta and the immaturity of the
newborn immune system, babies of mothers who develop varicella between five days before and two days after delivery should
also be given VZIG.
Varicella
Varicella (chicken pox) is caused by a herpes virus, varicellazoster virus. The highest incidence is in young children, although
non-immune adults are also at risk. It is highly infectious and the
chance of a second household member becoming infected is
80e95%. Although the disease is spread primarily by respiratory
droplets, the vesicle fluid is also infectious.
The prodromal period consists of fever, cough, coryza and
sore throat, and is followed by an intensely pruritic rash. Initially
papular, the lesions develop into clusters of vesicles that spread
from the face and trunk to the limbs, occasionally becoming
haemorrhagic (Figure 2). New crops of vesicles develop every
few days until they crust over and lesions exist concurrently at
several different stages. Secondary bacterial infection, usually in
the form of otitis media or group A streptococcal cellulitis, occurs
Figure 1 Measles.
MEDICINE 37:12
Figure 2 Haemorrhagic varicella.
687
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VIRAL INFECTIONS
After primary infection, varicella-zoster virus exists latently in
the sensory ganglia and can reactivate, particularly in the
immunocompromised and elderly, as herpes zoster (shingles).
This manifests as clusters of vesicles in one or two contiguous
dermatomes and can be painful. In adults, treatment with aciclovir is recommended within 72 h of onset to prevent the
complication of post-herpetic neuralgia, a very uncommon
sequela in children. In immunocompromised individuals, intravenous aciclovir should be started to prevent dissemination of
varicella, which has a high morbidity.
A specific manifestation of herpes zoster, Ramsay Hunt
syndrome, affects the VIIth cranial nerves. Individuals present
with a facial palsy, and vesicles may be seen on the pinna and in
the auditory canal. Although aciclovir and corticosteroids are
variously used for treatment, there is no good evidence for their
use, as trials of treatment for facial palsy have either excluded
Ramsay Hunt syndrome15,16 or have been too small to allow
a conclusion to be drawn.17
Vaccines against varicella have been available for a few years
although currently these are not part of the UK childhood
immunization schedule. Vaccination of non-immune household
contacts of immunocompromised patients is often advocated. A
combined varicella and MMR vaccine is used in Europe.18
foetal death. Intrauterine transfusions can prevent some of the
most severe outcomes if hydrops is diagnosed early.19
A second exanthem caused by erythrovirus B19 is papularpurpuric gloves and socks syndrome, a self-limiting condition
affecting children and young adults, first described in 1990.20
Erythema, oedema and pruritus of the hands and feet in a glove
and sock distribution are associated with mild fever. The
erythema progresses to petechiae and purpura on the palms and
soles, which may be painful. In addition to erythrovirus B19,
human herpes virus 6 (HHV6), HHV7, CMV and measles virus
have been implicated in the aetiology. Treatment is symptomatic
with antihistamines, and the rash usually resolves in 1e2 weeks
without sequelae.
Roseola infantum
The first virus to be associated with roseola infantum (sixth
disease, exanthem subitum) was HHV6, although it is also
caused by HHV7. These viruses are spread through contact with
saliva.
Roseola infantum affects infants and young children and is
characterized by a high fever for about three days, which
defervesces abruptly with the appearance of a pink maculopapular rash. The abrupt rise in temperature may be associated with febrile convulsions. Gastrointestinal and occasionally
respiratory symptoms can occur. Other clinical findings include
mild oedema and, occasionally, erythematous papules on the soft
palate (Nagayama spots). Complications are rare, but include
encephalitis, hepatitis and haemophagocytic syndrome. In the
occasional adult who develops roseola, it presents as a mononucleosis-like illness. Reactivation in children and adults who are
immunocompromised with high viral loads is significantly
associated with mortality after bone marrow transplantation.21
Treatment of roseola infantum is supportive, although ganciclovir and cidofovir have been used to treat reactivation of
HHV6 in immunocompromised individuals.22,23
Erythema infectiosum
Erythema infectiosum (fifth disease, slapped cheek syndrome) is
caused by erythrovirus (formerly parvovirus) B19. It is spread
via respiratory droplets and predominantly affects preschool
children although adults can be affected.
Around half of infections with erythrovirus B19 are asymptomatic. Erythema infectiosum has a mild prodromal period with
fever and malaise. The characteristic exanthem is a symmetrical
erythematous rash over both cheeks, and the trunk and limbs may
also develop a lacy maculopapular rash (Figure 3). Adults develop
a flu-like illness and are more likely to develop arthralgias than
children. Complications of erythrovirus B19 infection relate to its
tropism for pro-erythrocytes, causing anaemia. This can lead to
aplastic crises, particularly in those with underlying haemolytic
diseases. In immunocompromised individuals infection may
persist, leading to severe relapsing remitting anaemia. Infection in
non-immune pregnant women can cause hydrops foetalis and
Hand, foot and mouth disease
Hand, foot and mouth disease is caused by enteroviruses, most
commonly Coxsackie virus A16 and enterovirus 71. It is highly
contagious and is spread by the faecal-oral route, respiratory
droplets and contact with skin lesions. It predominates in preschool age children and outbreaks in nurseries are common.24
Incidence peaks in summer and autumn in temperate climates.
There is a prodrome lasting 1e2 days before the rash appears of
low-grade fever, anorexia and a sore mouth. Lesions initially
appear in the mouth as erythematous lesions on the buccal mucosa
and hard palate that become vesicular and ulcerate. Most individuals also develop vesicles with an erythematous base on the
palms, soles and in between the digits that can be itchy. A macular
rash may also appear on the trunk, buttocks and genitalia. The
rash usually resolves in 3e6 days. Treatment is supportive, in
particular for painful stomatitis, which may lead to dehydration.
Coxsackie viruses and echoviruses also cause herpangina,
which has lesions similar to those in hand, foot and mouth
disease but which are limited to the posterior oral cavity, with
none on the hands or feet. Enteroviruses can cause several
different types of rash e maculopapular, vesicular, urticarial and
petechial.
Figure 3 Erythema infectiosum.
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Ó 2009 Elsevier Ltd. All rights reserved.
VIRAL INFECTIONS
Rare complications of enteroviral infection include meningitis,
encephalitis, pneumonitis and myocarditis. Spontaneous abortion has been reported during infection in pregnancy, and
infection in late pregnancy can lead to severe disease in the
newborn clinically resembling bacterial sepsis.25
GianottieCrosti syndrome
GianottieCrosti syndrome (papular acrodermatitis of childhood)
was originally described in association with hepatitis B infection.
The commonest cause, however, is EpsteineBarr virus (EBV),
and other infectious agents have been implicated, including
enteroviruses, various respiratory viruses, erythrovirus B19 and
cytomegalovirus (CMV). There are a few reports of Gianottie
Crosti syndrome following immunizations.26,27
It is generally a self-limiting condition usually lasting 10e14
days and predominantly affecting preschool children. In adults, it
is rare and exclusive to women. The exanthem is an erythematous papular or vesicular rash affecting the extensor surface of
the extremities, face and buttocks, which may be pruritic. The
rash is often asymmetrical and lesions may coalesce to form
plaques. It is associated with fever and/or lymphadenopathy in
about one-third of individuals. Occasionally acute hepatitis
develops, particularly when the causative organism is hepatitis
B, EBV or CMV, and very rarely this can become chronic.
Treatment is symptomatic.
EBV is also the causative virus in infectious mononucleosis
(glandular fever). Classically, the symptoms are fever, sore
throat, fatigue and enlarged lymph nodes, with exanthem only
rarely described. However, if amoxicillin is prescribed for
presumed bacterial tonsillitis, a florid widespread maculopapular
rash can develop (Figure 4).
Figure 4 EBV and amoxicillin.
trunk. It can be pruritic, and treatment with antihistamines
provides symptomatic relief. The rash usually resolves within
several weeks without treatment. Ultraviolet light has been used
anecdotally to shorten the course in pityriasis, but comparative
studies in a few patients have not shown good evidence for its
use.29
Unilateral laterothoracic exanthem
Also known as asymmetric periflexural exanthem of childhood,
unilateral laterothoracic exanthem was described in 18 patients
in 1992.28 It usually occurs in winter and early spring and is most
common in children aged 1e5 years, although it has been
reported rarely in adults. No single causative organism has been
identified although erythrovirus B19 and EBV have been associated. It has been suggested that it is a skin eruption common to
several different viruses.
There is usually a prodrome of low-grade fever and mild
respiratory and gastrointestinal symptoms. The rash begins
unilaterally on the trunk, most frequently in the axilla and can
be accompanied by an enlarged axillary lymph node. It is
a morbilliform or eczematous rash that may spread bilaterally
but retains a unilateral predominance. It is self-limiting and
usually resolves in about four weeks without complication.
Pityriasis rosea
These exanthems should be differentiated from rashes associated with bacterial infection, such as meningococcal septicaemia, scarlet fever, toxic shock syndrome and staphylococcal
scalded skin syndrome, rickettsial tick-borne diseases, such as
Lyme disease, and Kawasaki disease. In addition, it is important
to consider non-infectious causes, such as HenocheSchönlein
purpura, juvenile idiopathic arthritis, leukaemia and drug
exposure.
Viral exanthems are often difficult to differentiate from each
other even after careful history-taking and examination. The
availability of PCR has greatly increased diagnostic accuracy, but
results are rarely available immediately. Although most viral
exanthems are benign and self-limiting, it is important to treat
potentially life-threatening diseases in the differential diagnosis
urgently.
A
Pityriasis rosea is an exanthem of unknown cause affecting older
children and young adults. A viral cause is suggested by seasonal
and geographical clustering.
A sore throat can precede the exanthem, and constitutional
symptoms such as headache and low-grade fever can accompany
the rash. The rash is characterized by pink or red scaly oval
lesions, often preceded by a single lesion, predominantly on the
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FURTHER READING
Pickering LK, ed. Red Book: 2006 Report of the Committee on Infectious
Diseases. 27th edn. American Academy of Pediatrics; 2006 (The
definitive quick reference text of paediatric infectious diseases).
The green book e immunisations against infectious disease. Department
of Health; 2006 (Immunization advice in the UK).
www.hpa.org.uk (The Health Protection Agency website for the current
status of various infectious diseases).
http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/
Greenbook/dh_4097254 (The Green Book online).
aapredbook.aappublications.org (The Red Book online).
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